HGG Advances最新文献_第2页

Letter to the Editor: Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection. 致编辑的信：经典HLA基因与无症状SARS-CoV-2感染之间缺乏关联。

IF 3.3

HGG Advances Pub Date : 2024-11-02 DOI: 10.1016/j.xhgg.2024.100382

Eleanor Karp-Tatham, Callum R O'Neill, Julian C Knight, Alexander J Mentzer, Amanda Y Chong

引用次数: 0

RLIM-specific activity reporters define variant pathogenicity in Tonne-Kalscheuer syndrome. RLIM 特异性活性报告确定了 Tonne-Kalscheuer 综合征的变异致病性。

IF 3.3

HGG Advances Pub Date : 2024-10-31 DOI: 10.1016/j.xhgg.2024.100378

Venkateshwarlu Bandi, Martin Rennie, Intisar Koch, Polly Gill, Oscar D Pacheco, Aaron D Berg, Hong Cui, D Isum Ward, Francisco Bustos

{"title":"RLIM-specific activity reporters define variant pathogenicity in Tonne-Kalscheuer syndrome.","authors":"Venkateshwarlu Bandi, Martin Rennie, Intisar Koch, Polly Gill, Oscar D Pacheco, Aaron D Berg, Hong Cui, D Isum Ward, Francisco Bustos","doi":"10.1016/j.xhgg.2024.100378","DOIUrl":"10.1016/j.xhgg.2024.100378","url":null,"abstract":"Tonne-Kalscheuer syndrome (TOKAS; MIM: 300978) is an X-linked recessive disorder with devastating consequences for patients, such as intellectual disability, developmental delay, and multiple congenital abnormalities. TOKAS is associated with hemizygous variants in the RLIM gene, which encodes a RING-type E3 ubiquitin ligase. The current sustained increase in reported RLIM variants of uncertain significance creates an urgent need to develop assays that can screen these variants and experimentally determine their pathogenicity and disease association. Here, we engineered flow cytometry-based RLIM-specific reporters to measure RLIM activity in TOKAS. This paper describes the design and use of RLIM-specific reporters to determine the pathogenicity of a TOKAS RLIM gene variant. Our data demonstrate that RLIM-specific flow cytometry reporters based on either the full length or a degron region of the substrate REX1 measure RLIM activity in cells. Further, we describe the TOKAS variant RLIM p.Asn581Lys and, using reporter assays, determine that it disrupts RLIM catalytic activity. These data reveal how the p.Asn581Lys variant impairs RLIM function and suggests pathogenic mechanisms. The use of RLIM-specific reporters will greatly accelerate the resolution of variants of uncertain significance and disease association in TOKAS.","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100378"},"PeriodicalIF":3.3,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epileptic encephalopathy linked to a DALRD3 missense variant that impairs tRNA modification. 癫痫性脑病与影响 tRNA 修饰的 DALRD3 错义变体有关。

IF 4.3

HGG Advances Pub Date : 2024-10-31 DOI: 10.1016/j.xhgg.2024.100377

Kejia Zhang, Katharina Löhner, Henny H Lemmink, Maartje Boon, Jenna M Lentini, Naduni de Silva, Dragony Fu

{"title":"Epileptic encephalopathy linked to a DALRD3 missense variant that impairs tRNA modification.","authors":"Kejia Zhang, Katharina Löhner, Henny H Lemmink, Maartje Boon, Jenna M Lentini, Naduni de Silva, Dragony Fu","doi":"10.1016/j.xhgg.2024.100377","DOIUrl":"10.1016/j.xhgg.2024.100377","url":null,"abstract":"Epileptic encephalopathies are severe epilepsy syndromes characterized by early onset and progressive cerebral dysfunction. A nonsense variant in the DALR anticodon binding domain containing 3 (DALRD3) gene has been implicated in epileptic encephalopathy, but no other disease-associated variants in DALRD3 have been described. In human cells, the DALRD3 protein forms a complex with the METTL2 methyltransferase to generate the 3-methylcytosine (m3C) modification in specific arginine tRNAs. Here, we identify an individual with a homozygous missense variant in DALRD3 who displays developmental delay, cognitive deficiencies, and multifocal epilepsy. The missense variant substitutes an arginine residue to cysteine (R517C) within the DALR domain of the DALRD3 protein that is required for binding tRNAs. Cells derived from the individual homozygous for the DALRD3-R517C variant exhibit reduced levels of m3C modification in arginine tRNAs, indicating that the R517C variant impairs DALRD3 function. Notably, the DALRD3-R517C protein displays reduced association with METTL2 and loss of interaction with substrate tRNAs. Our results uncover another loss-of-function variant in DALRD3 linked to epileptic encephalopathy disorders. Importantly, these findings underscore DALRD3-dependent tRNA modification as a key contributor to proper brain development and function.","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100377"},"PeriodicalIF":4.3,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advancements in genetic research by the Hispanic Community Health Study/Study of Latinos: A 10-year retrospective review. 西班牙裔社区健康研究/拉丁裔研究（HCHS/SOL）在基因研究方面取得的进展：十年回顾

IF 3.3

HGG Advances Pub Date : 2024-10-29 DOI: 10.1016/j.xhgg.2024.100376

Hridya Rao, Margaret C Weiss, Jee Young Moon, Krista M Perreira, Martha L Daviglus, Robert Kaplan, Kari E North, Maria Argos, Lindsay Fernández-Rhodes, Tamar Sofer

引用次数: 0

Functional genomics implicates natural killer cells in the pathogenesis of ankylosing spondylitis. 功能基因组学发现自然杀伤细胞与强直性脊柱炎的发病机制有关。

IF 3.3

HGG Advances Pub Date : 2024-10-28 DOI: 10.1016/j.xhgg.2024.100375

Marcos Chiñas, Daniela Fernandez-Salinas, Vitor R C Aguiar, Victor E Nieto-Caballero, Micah Lefton, Peter A Nigrovic, Joerg Ermann, Maria Gutierrez-Arcelus

{"title":"Functional genomics implicates natural killer cells in the pathogenesis of ankylosing spondylitis.","authors":"Marcos Chiñas, Daniela Fernandez-Salinas, Vitor R C Aguiar, Victor E Nieto-Caballero, Micah Lefton, Peter A Nigrovic, Joerg Ermann, Maria Gutierrez-Arcelus","doi":"10.1016/j.xhgg.2024.100375","DOIUrl":"10.1016/j.xhgg.2024.100375","url":null,"abstract":"Multiple lines of evidence indicate that ankylosing spondylitis (AS) is a lymphocyte-driven disease. However, which lymphocyte populations are critical in AS pathogenesis is not known. In this study, we aimed to identify the key cell types mediating the genetic risk in AS using an unbiased functional genomics approach. We integrated genome-wide association study (GWAS) data with epigenomic and transcriptomic datasets of human immune cells. To quantify enrichment of cell type-specific open chromatin or gene expression in AS risk loci, we used three published methods-LDSC-SEG, SNPsea, and scDRS-that have successfully identified relevant cell types in other diseases. Natural killer (NK) cell-specific open chromatin regions are significantly enriched in heritability for AS, compared to other immune cell types such as T cells, B cells, and monocytes. This finding was consistent between two AS GWAS. Using RNA sequencing data, we validated that genes in AS risk loci are enriched in NK cell-specific gene expression. Using the human Space-Time Gut Cell Atlas, we also found significant upregulation of AS-associated genes predominantly in NK cells. We performed co-localization analyses between GWAS risk loci and genetic variants associated with gene expression (eQTL) to find putative target genes. This revealed four AS risk loci affecting regulation of candidate target genes in NK cells: two known loci, ERAP1 and TNFRSF1A, and two understudied loci, ENTR1 (SDCCAG3) and B3GNT2. Our findings suggest that NK cells may play a crucial role in AS development and highlight four putative target genes for functional follow-up in NK cells.","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100375"},"PeriodicalIF":3.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Variants in the β-globin Locus are Associated with Pneumonia in African American Children. β-球蛋白基因座变异与非裔美国儿童肺炎有关。

IF 3.3

HGG Advances Pub Date : 2024-10-22 DOI: 10.1016/j.xhgg.2024.100374

Nadine L N Halligan, Sarah C Hanks, Karen Matsuo, Taylor Martins, Sebastian Zöllner, Michael W Quasney, Laura J Scott, Mary K Dahmer

{"title":"Variants in the β-globin Locus are Associated with Pneumonia in African American Children.","authors":"Nadine L N Halligan, Sarah C Hanks, Karen Matsuo, Taylor Martins, Sebastian Zöllner, Michael W Quasney, Laura J Scott, Mary K Dahmer","doi":"10.1016/j.xhgg.2024.100374","DOIUrl":"https://doi.org/10.1016/j.xhgg.2024.100374","url":null,"abstract":"In African American adults, the strongest genetic predictor of pneumonia appears to be the A allele of rs334, a variant in the β-globin gene which in homozygous form causes sickle cell disease (SCD). No comparable studies have been done in African American children. We performed genome-wide association analyses of 482 African American children with documented pneumonia and 2048 African American controls using genotypes imputed from two reference panels: 1000 Genomes (1KG) (which contains rs334) and TOPMed (does not contain rs334). Using 1KG imputed genotypes, the most significant variant was rs334 (A allele (OR = 2.76 (2.21-3.74), p=5.9x10-19); using TOPMed imputed genotypes the most significant variant was rs2226952, found in the β-globin locus control region (G allele (OR =2.14 (1.78-2.57), p = 5.1x10-16). After conditioning on rs334, the most strongly associated variant in the β-globin locus was rs33930165, (allele T, 1KG: OR=4.09 (2.29-7.29), p=1.7x10-6; TOPMed: OR=3.58 (2.18-5.90), p=4.7x10-7), which as a compound heterozygote with rs334 A allele can cause SCD. To compare the power of different sample sets we developed a way to estimate the power of sample sets with different sample sizes, genotype arrays and imputation platforms. Our results suggest that in African American children the strongest genetic determinants of pneumonia are those that increase the risk of SCD.","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100374"},"PeriodicalIF":3.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HCV- and HBV-mediated liver cancer converge on similar transcriptomic landscapes and immune profiles. HCV和HBV介导的肝癌具有相似的转录组景观和免疫特征。

IF 3.3

HGG Advances Pub Date : 2024-10-19 DOI: 10.1016/j.xhgg.2024.100373

Elizabeth S Borden, Annika Jorgensen, Heini M Natri, Karen Taraszka Hastings, Kenneth H Buetow, Melissa A Wilson

{"title":"HCV- and HBV-mediated liver cancer converge on similar transcriptomic landscapes and immune profiles.","authors":"Elizabeth S Borden, Annika Jorgensen, Heini M Natri, Karen Taraszka Hastings, Kenneth H Buetow, Melissa A Wilson","doi":"10.1016/j.xhgg.2024.100373","DOIUrl":"10.1016/j.xhgg.2024.100373","url":null,"abstract":"Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths worldwide, and a large proportion is attributable to viral causes, including hepatitis B (HBV) and C viruses (HCV). The pathogenesis of viral-mediated HCC can differ between HBV and HCV, but it is unclear how much these differences influence the tumors' final molecular and immune profiles. Additionally, there are known sex differences in the molecular etiology of HCC, but sex differences have not been explored in the context of viral-mediated HCC. To determine the extent to which the viral status and sex impact the molecular and immune profiles of HCC, we performed differential expression and immune cell deconvolution analyses. We identified a large number of differentially expressed genes unique to the HBV or HCV tumor:tumor-adjacent comparison. Pathway enrichment analyses demonstrated that changes unique to the HCV tumor:tumor-adjacent tissue were dominated by changes in immune pathways. Immune cell deconvolution demonstrated that HCV tumor-adjacent tissue had the largest immune cell infiltrate, with no difference in the immune profiles within HBV and HCV tumor samples. Overall, this work demonstrates the convergence of HBV- and HCV-mediated HCC on a similar transcriptomic landscape and immune profile despite differences in the surrounding tissue.","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100373"},"PeriodicalIF":3.3,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LSM7 variants involving key amino acids for LSM complex function cause a neurodevelopmental disorder with leukodystrophy and cerebellar atrophy. 涉及 LSM 复合物功能关键氨基酸的 LSM7 变体会导致一种伴有白营养不良和小脑萎缩的神经发育障碍。

IF 3.3

HGG Advances Pub Date : 2024-10-16 DOI: 10.1016/j.xhgg.2024.100372

Matis Crespin, Karine Siquier-Pernet, Pauline Marzin, Christine Bole-Feysot, Valérie Malan, Patrick Nitschké, Marie Hully, Charles-Joris Roux, Michel Lemoine, Marlène Rio, Nathalie Boddaert, Thomas Courtin, Vincent Cantagrel

{"title":"LSM7 variants involving key amino acids for LSM complex function cause a neurodevelopmental disorder with leukodystrophy and cerebellar atrophy.","authors":"Matis Crespin, Karine Siquier-Pernet, Pauline Marzin, Christine Bole-Feysot, Valérie Malan, Patrick Nitschké, Marie Hully, Charles-Joris Roux, Michel Lemoine, Marlène Rio, Nathalie Boddaert, Thomas Courtin, Vincent Cantagrel","doi":"10.1016/j.xhgg.2024.100372","DOIUrl":"10.1016/j.xhgg.2024.100372","url":null,"abstract":"Cerebellar atrophy and hypoplasia are usually identified on MRI performed on children presenting signs of cerebellar ataxias, developmental delay, and intellectual disability. These signs can be associated with hypo- or de-myelinating leukodystrophies. A recent study reported two cases: one child diagnosed with leukodystrophy and cerebellar atrophy, harboring a homozygous variant in LSM7, and another who died in utero, presumed to have another homozygous variant in LSM7, based on the parents' genotype. LSM7 encodes a subunit of the LSM complex, involved in pre-RNA maturation and mRNA degradation. Consequently, it has been suggested as a strong candidate disease gene. This hypothesis was supported by functional investigations of the variants. Here, we report a patient with neurodevelopmental defects, leukodystrophy, and cerebellar atrophy, harboring compound heterozygous missense variants in the LSM7 gene. One of these variants is the same as the one carried by the first case reported previously. The other one is at the same position as the variant potentially carried by the second case reported previously. Based on comparable neuroimaging, clinical features, and the involvement of the same amino acids previously demonstrated as key for LSM complex function, we confirm that LSM7 disruption causes a neurodevelopmental disorder characterized by leukodystrophy and cerebellar atrophy.","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100372"},"PeriodicalIF":3.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LARP1 haploinsufficiency is associated with an autosomal dominant neurodevelopmental disorder. LARP1 单倍体缺乏症与一种常染色体显性神经发育障碍有关。

IF 3.3

HGG Advances Pub Date : 2024-10-10 Epub Date: 2024-08-30 DOI: 10.1016/j.xhgg.2024.100345

James Chettle, Raymond J Louie, Olivia Larner, Robert Best, Kevin Chen, Josephine Morris, Zinaida Dedeic, Anna Childers, R Curtis Rogers, Barbara R DuPont, Cindy Skinner, Sébastien Küry, Kevin Uguen, Marc Planes, Danielle Monteil, Megan Li, Aviva Eliyahu, Lior Greenbaum, Nofar Mor, Thomas Besnard, Bertrand Isidor, Benjamin Cogné, Alyssa Blesson, Anne Comi, Ingrid M Wentzensen, Blake Vuocolo, Seema R Lalani, Roberta Sierra, Lori Berry, Kent Carter, Stephan J Sanders, Sarah P Blagden

{"title":"LARP1 haploinsufficiency is associated with an autosomal dominant neurodevelopmental disorder.","authors":"James Chettle, Raymond J Louie, Olivia Larner, Robert Best, Kevin Chen, Josephine Morris, Zinaida Dedeic, Anna Childers, R Curtis Rogers, Barbara R DuPont, Cindy Skinner, Sébastien Küry, Kevin Uguen, Marc Planes, Danielle Monteil, Megan Li, Aviva Eliyahu, Lior Greenbaum, Nofar Mor, Thomas Besnard, Bertrand Isidor, Benjamin Cogné, Alyssa Blesson, Anne Comi, Ingrid M Wentzensen, Blake Vuocolo, Seema R Lalani, Roberta Sierra, Lori Berry, Kent Carter, Stephan J Sanders, Sarah P Blagden","doi":"10.1016/j.xhgg.2024.100345","DOIUrl":"10.1016/j.xhgg.2024.100345","url":null,"abstract":"Autism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) that affects approximately 4% of males and 1% of females in the United States. While causes of ASD are multi-factorial, single rare genetic variants contribute to around 20% of cases. Here, we report a case series of seven unrelated probands (6 males, 1 female) with ASD or another variable NDD phenotype attributed to de novo heterozygous loss of function or missense variants in the gene LARP1 (La ribonucleoprotein 1). LARP1 encodes an RNA-binding protein that post-transcriptionally regulates the stability and translation of thousands of mRNAs, including those regulating cellular metabolism and metabolic plasticity. Using lymphocytes collected and immortalized from an index proband who carries a truncating variant in one allele of LARP1, we demonstrated that lower cellular levels of LARP1 protein cause reduced rates of aerobic respiration and glycolysis. As expression of LARP1 increases during neurodevelopment, with higher levels in neurons and astrocytes, we propose that LARP1 haploinsufficiency contributes to ASD or related NDDs through attenuated metabolic activity in the developing fetal brain.","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100345"},"PeriodicalIF":3.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Copy-number variants differ in frequency across genetic ancestry groups. 不同基因祖先群体的拷贝数变异频率不同。

IF 3.3

HGG Advances Pub Date : 2024-10-10 Epub Date: 2024-08-12 DOI: 10.1016/j.xhgg.2024.100340

Laura M Schultz, Alexys Knighton, Guillaume Huguet, Zohra Saci, Martineau Jean-Louis, Josephine Mollon, Emma E M Knowles, David C Glahn, Sébastien Jacquemont, Laura Almasy

引用次数: 0